Background: TKI-acquired resistance is a tough obstacle for effectively treating NSCLC patients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation.
Methods: We detected TGF-β1and PTEN expression levels in 51 NSCLC patients undergoing EGFR-TKI treatment using Immunohistochemistry (IHC) assay. We examined erlotinib sensitivity, apoptosis rate, and invasion ability in PC-9 cells and PC-9/TGF-β1 cells with CCK-8, flow cytometry, and trans-well assays. We examined and analyzed the AKT and ERK pathways' expression levels using western blot.
Results: High TGF-β1 and low PTEN expression levels were correlated with poor EGFR-TKI sensitivity and overall survival in 51 NSCLC samples. In vitro analysis revealed that TGF-β1 could reduce erlotinib sensitivity, increase anti-apoptosis ability and invasive characteristic in TKI-sensitive PC-9 cell lines by down-regulating PTEN and activating the Akt and ERK pathways.
Conclusions: The results suggest that TGF-β1 demonstrated another acquired erlotinib resistance by down-regulating PTEN expression.
Keywords: Erlotinib; NSCLC; TGF-β1; TKI resistance.
Copyright © 2015. Published by Elsevier Masson SAS.